Resonant Waveguide Grating Biosensor for Living Cell Sensing

Abstract

This article presents theoretical analysis and experimental data for the use of resonant waveguide grating (RWG) biosensors to characterize stimulation-mediated cell responses including signaling. The biosensor is capable of detecting redistribution of cellular contents in both directions that are perpendicular and parallel to the sensor surface. This capability relies on online monitoring cell responses with multiple optical output parameters, including the changes in incident angle and the shape of the resonant peaks. Although the changes in peak shape are mainly contributed to stimulation-modulated inhomogeneous redistribution of cellular contents parallel to the sensor surface, the shift in incident angle primarily reflects the stimulation-triggered dynamic mass redistribution (DMR) perpendicular to the sensor surface. The optical signatures are obtained and used to characterize several cellular processes including cell adhesion and spreading, detachment and signaling by trypsinization, and signaling through either epidermal growth factor receptor or bradykinin B2 receptor. A mathematical model is developed to link the bradykinin-mediated DMR signals to the dynamic relocation of intracellular proteins and the receptor internalization during B2 receptor signaling cycle. This model takes the form of a set of nonlinear, ordinary differential equations that describe the changes in four different states of B2 receptors, diffusion of proteins and receptor-protein complexes, and the DMR responses. Classical analysis shows that the system converges to a unique optical signature, whose dynamics (amplitudes, transition time, and kinetics) is dependent on the bradykinin signal input, and consistent with those observed using the RWG biosensors. This study provides fundamentals for probing living cells with the RWG biosensors, in general, optical biosensors.

Microfluidic channels laser-cut in thin double-sided tapes: Cost-effective biocompatible fluidics in minutes from design to final integration with optical biochips

“…The need for reliable, cheap, disposable lab-on-a-chip and point-of-care devices is on the rise [1][2][3][4][5]. These systems are utilized in biotechnology, medical treatment and diagnosis, and in basic research as well [6,7].…”

Bulk and surface sensitivity of a resonant waveguide grating imager

“…[http://dx.doi.org/10.1063/1.4866460] Label-free optical biosensors include surface plasmon resonance (SPR), 1 optical waveguide lightmode spectroscopy (OWLS), 2 photonic crystal (PC) biosensor, 3 and resonant waveguide grating (RWG), 4,5 all of which employ surface bound evanescent waves to characterize processes accompanied by refractive index variations close to the sensor surface (100-200 nm). 6 These biosensors, although divergent in throughput and operational schemes, have found widespread applications for both biomolecular interaction analysis 7,8 and cell phenotypic profiling.…”

Counting cells with a low-cost integrated microfluidics-waveguide sensor

“…2 Waveguides are optical structures that guide light by total internal reflection. Waveguides have been in extensive use in the telecommunications industry, and have made inroads in the field of biological and chemical sensing, [3][4][5][6][7][8][9][10][11][12][13][14][15] but have made only a limited entry into actual clinical diagnostics. 16 Typically, the evanescent field of the waveguide has been exploited, sensing a change in the refractive index of an overlying material as a change in the effective index of the waveguide.…”